ArticleCancer cell2018
Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic Drivers in Hürthle Cell Carcinoma.
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Article in Cancer cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 2 of them syntheses that pooled it.
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134citing papers in PubMed, 2 pooled it
7.8field-weighted citation impact, top 1% of its field
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Who cites it
134 citing papers in PubMed, 2 syntheses or guidelines pooled it, 258 citations in OpenAlex.
- 2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer.Thyroid : official journal of the American Thyroid Association · 2025Guideline
- Hürthle Cell Carcinoma of the Thyroid Gland: Systematic Review and Meta-analysis.Advances in therapy · 2021Pooled it
- Molecular Diagnostics and [Thyroid : official journal of the American Thyroid Association · 2024Trial
- [European journal of nuclear medicine and molecular imaging · 2022Trial
- Article
- RAC1 signaling in polyploid giant cancer cells: Implications for tumorigenesis and therapy resistance.Cancer letters · 2026Review
- Genomics and Multi-Omics to Guide Clinical Management in Thyroid Cancer.International journal of molecular sciences · 2026Review
- Mitochondrial transfer technologies with molecular insights into clinical applications.Stem cells (Dayton, Ohio) · 2026Review
- Loss of heterozygosity exposes germline mutations in complex I and drives Warburg metabolism in oncocytic carcinoma of the thyroid.Science advances · 2026Article
- Distinct ALK Expression Patterns Are Associated with Canonical and Noncanonical STRN::ALK Transcript Architectures in Oncocytic Thyroid Neoplasms.Endocrine pathology · 2026Article
- Impact of mitochondrial reductive stress due to respiratory chain limitation on cancer via posttranslational modifications.Redox biology · 2026Review
- Review
- Integrative transcriptomics and electrophysiological profiling of hiPSC-derived neurons identifies novel druggable pathways in Koolen-de Vries Syndrome.Molecular psychiatry · 2026Article
- Pervasive chromosomal instability drives the karyotypic evolution of hypodiploid tumours.Genome medicine · 2026Article
- Mitochondrial DNA mutations and intercellular mitochondrial transfer in cancer: mechanisms, biological effects, and clinical potential.Biomarker research · 2026Review
- State of the Art on Thyroid Cancer Biology and Oncology.Biomedicines · 2026Review
- Review
- Loss of heterozygosity exposes germline mutations in complex I and drives Warburg metabolism in oncocytic carcinoma of the thyroid.bioRxiv : the preprint server for biology · 2025Article
- Diagnosing the silent: the molecular landscape of non-functional parathyroid carcinoma.Virchows Archiv : an international journal of pathology · 2025Review
- Review
74 more citing papers are in PubMed but not listed here.
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Authors and funding
31 authors at 4 institutions in 1 country.
Raj K GopalDepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Harvard Medical School, Boston, MA 02115, USA.
Kirsten KüblerCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA.
Sarah E CalvoDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Paz PolakCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA.
Dimitri LivitzBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Daniel RosebrockBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Peter M SadowCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
Braidie CampbellDepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Samuel E DonovanDepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Salma AminCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Benjamin J GigliottiDepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Zenon GrabarekDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Julian M HessBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Chip StewartBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Lior Z BraunsteinBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Peter F ArndtBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Scott MordecaiDepartment of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Angela R ShihDepartment of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
Frances ChavesDepartment of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Tiannan ZhanInstitute for Technology Assessment, Massachusetts General Hospital, Boston, MA 02114, USA.
Carrie C LubitzCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA; Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
Jiwoong KimDepartment of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
A John IafrateDepartment of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
Lori WirthDepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
Sareh ParangiCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
Ignaty LeshchinerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Gilbert H DanielsDepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Thyroid Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
Vamsi K MoothaDepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Dora Dias-SantagataDepartment of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
Gad GetzCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: gadgetz@broadinstitute.org.
David G McFaddenDepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Thyroid Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: david.mcfadden@utsouthwestern.edu.
Broad Institute · USHarvard University · USMassachusetts General Hospital · USThe University of Texas Southwestern Medical Center · US
Funding
Treating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Wanling Xie · 2003 to 2026
$53.4MThe Role of BRAF Mutation in Thyroid Cancer InvasionR01CA149738 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI PARANGI, SAREH · 2011 to 2015
$1.6M"Comparative gene resequencing in mouse cancer models"K08CA160658 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI MCFADDEN, DAVID GLENN · 2011 to 2015
$900kImageStream X Analyzer 2011S10OD012027 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2012 to 2012
$595kHoward Hughes Medical InstituteNCI NIH HHS K08 CA160658NCI NIH HHS P50 CA101942NCI NIH HHS R01 CA149738NIH HHS S10 OD012027
Abstract
Hürthle cell carcinoma of the thyroid (HCC) is a form of thyroid cancer recalcitrant to radioiodine therapy that exhibits an accumulation of mitochondria. We performed whole-exome sequencing on a cohort of primary, recurrent, and metastatic tumors, and identified recurrent mutations in DAXX, TP53, NRAS, NF1, CDKN1A, ARHGAP35, and the TERT promoter. Parallel analysis of mtDNA revealed recurrent homoplasmic mutations in subunits of complex I of the electron transport chain. Analysis of DNA copy-number alterations uncovered widespread loss of chromosomes culminating in near-haploid chromosomal content in a large fraction of HCC, which was maintained during metastatic spread. This work uncovers a distinct molecular origin of HCC compared with other thyroid malignancies.
Indexed as
Chromosome AberrationsMutationDNA Copy Number VariationsDNA, MitochondrialExome SequencingHaploidyHumansNeoplasm MetastasisTelomeraseThyroid NeoplasmsDNA, MitochondrialTelomeraseTERT protein, humanchromosomal lossescomplex IhaploidHürthle cellloss of heterozygositymetastasismitochondriamtDNAoncocyticthyroid cancer
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